Detailing hydrogen bonding and deprotonation equilibria between anions and urea/thiourea derivatives

Spectrophotometric and 1H NMR titrations of N-methoxyethyl-N'-(4-nitrophenyl)thiourea (3) by Bu(4-)NOAc show that in DMSO deprotonation of the receptor and formation of a hydrogen-bonded complex with anion proceed simultaneously but in MeCN deprotonation requires the participation of the second acetate anion. The formation constants of hydrogen-bonded complexes were determined from titrations in the presence of added acetic acid, which suppressed deprotonation. These constants together with independently measured stability constants of (AcO)(2)H(-) complexes were employed for a rigorous numerical analysis of titration results in the absence of added acid, which allowed us to determine the equilibrium deprotonation constants as well as pKa values for 3 in both solvents. Although 3 appeared to be a weaker acid than AcOH in both solvents, it can be deprotonated by acetate in dilute solutions when the concentration of liberated acetic acid is low enough. With disubstituted N,N-bis(methoxyethyl)-N'-(4-nitrophenyl)thiourea 4 only deprotonation equilibrium is observed. In contrast, both parent urea derivatives 1 and 2 cannot be deprotonated by acetate anions. Independent of the real type of equilibrium, whether it is a deprotonation or a hydrogen bonding, titration plots always can be satisfactorily fitted to a formal 1:1 binding isotherm. A relationship between apparent "binding constants" and real equilibrium constants of hydrogen bonding association and deprotonation processes is discussed.